1. Field of the Invention
The present invention relates to the field of nanoparticles such as carbon nanotubes and to the field of delivery of drugs to cells.
2. Related Art
Single-walled carbon nanotubes (SWNT) are novel polyaromatic molecules with ultra-high surface areas of ˜2600 m2/g. While sidewall functionalization has been actively pursued,1 little has been done to partition nanotube surfaces chemically and facilitate basic and practical applications for chemistry, biology and medicine.2-6 Accordingly, there is a need in the art for methods to partition nanotube surfaces.
Zheng, et al., “DNA-assisted dispersion and separation of carbon nanotubes” (2003) Nature Mater. 2: 338-342 describe the solubilization of carbon nanotubes by single stranded DNA molecules, wherein the DNA molecule wraps helically around the carbon nanotube through π-stacking interactions to form a soluble complex. See also, Zheng, et al., “Structure-Based Carbon Nanotube Sorting by Sequence-Dependent DNA Assembly,” Science 29:1545-1548 (November 2003).
Dai, et al., WO 02/095099, entitled “Noncovalent sidewall functionalization of carbon nanotubes” (published Nov. 28, 2002 and related to PNAS 100:4984 cited below, as well as US PGPUB 2005/0100960) relates to complexes formed from the irreversible adsorption of molecules to the sidewalls of carbon nanotubes through π-stacking, van der Waals and hydrophobic interactions. As shown in the US PGPUB 2005/0100960, a plurality of noncovalently-bonded molecules, having a highly aromatic group such as a pyrenyl group, are configured and arranged for bonding to additional molecules, e.g., biomolecules such as antibodies, antigens and DNA. These complexes are intended for in vitro use, e.g., as biosensors, where the attached molecules do not dissociate from the nanotubes.
Chen et al., “Noncovalent functionalization of nanotubes for highly specific electronic biosensors”, PNAS, 100:4984-4989 (2003) shows the binding of various proteins (Steptavidin, avidin, BSA, staphylococcal protein A and α-glucosidase) to as-grown nanotubes, and nanotubes treated with surfactants such as Tween, Pluronic P103 and Triton-X. It was reported that a monolayer of Tween 20 anchored on a nanotube would repel non-specific binding of proteins in solution. Ten different polypropylene oxide molecules were investigated for their ability to adsorb onto nanotube walls.
Hannah, US PGPUB 2004/0110128, published Jun. 10, 2004, entitled “Carbon Nanotube Molecular Labels,” discloses that carbon nanotubes may be derivatized with reactive groups to facilitate attachment to analytes or probes. Nanotubes may be derivatized to contain carboxylic acid groups (U.S. Pat. No. 6,187,823). Carboxylate derivatized nanotubes may be attached to nucleic acid probes or other analytes by standard chemistries, for example by carbodiimide mediated formation of an amide linkage with a primary or secondary amine group located on a probe or analyte. The methods of derivatization and cross-linking are not limiting and any reactive group or cross-linking methods known in the art may be used.
US PGPUB 20040038251 to Smalley, et al., published Feb. 26, 2004, entitled “Single-wall carbon nanotubes of precisely defined type and use thereof,” discloses that surfactants can also be used as non-perturbing coatings for suspending individual single-wall carbon nanotubes. The surfactant may be BRIJ® surfactants (polyethylene glycol dodecyl ether, polyethylene glycol lauryl ether, polyethylene glycol hexadecyl ether, polyethylene glycol stearyl ether, and polyethylene glycol oleyl ether), and other surfactants.
US PGPUB 20060014375 to Ford et al., published Jan. 19, 2006, entitled “Soluble carbon nanotubes,” discloses a method of solubilizing carbon nanotubes. Carbon nanotubes and urea are mixed together and then heated.
Dwyer, et al., “DNA functionalized single-walled carbon nanotubes,” Nanotechnology, 13:601-604 (2002) discloses linking DNA to nanotubes through amino-terminated DNA strands. A lambda DNA cluster is shown attached to a defect site and ends of an SWNT bundle.
Felekis, et al., “Single-walled carbon nanotube-based hybrid materials for managing charge transfer processes,” Rev. Adv. Mater. Sci., 10:272-276 (2005) discloses formation of nanohybrids consisting of SWNT units and electron donor moieties such as porpyrinic and ferrocenyl units.
Menna et al., in a conference paper dated Oct. 1, 2003, “Shortened single-walled nanotubes functionalized with poly(ethylene glycol): preparation and properties,” disclose the grafting of PEG onto SWNTs after acid oxidative cutting, treatment with SOCl2 to yield SWNT-COCL, and amidation with PEG-monoamine.
Kam et al. “Nanotube Molecular Transporters: Internalization of Carbon Nanotube-Protein Conjugates into Mammalian Cells,” J. Am. Chem. Soc., 126 (22), 6850-6851, (2004) discloses SWNT-protein conjugates delivered to cells. The authors used an oxidation/sonication procedure, which introduced surface carboxylates on the nanotubes for chemical derivatization. The carboxylic acid was treated with amino-biotin or a fluorescent label.
Zhang Liu, Weibo Cai, Lina He, Nozomi Nakayama, Kai Chen, Xiaoming Sun, Xiayuan Chen, Hongjie Dai. “In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice,” Nature Nanotechnology, Vol. 2, 47-52, January 2007 disclose the preparation of SWNTs, which were functionalized by the strong adsorption of phospholipids grafted onto amine-terminated polyethylene glycol. Thiol-modified siRNA cargo molecules were linked to the amine groups on the sidewalls of SWNTs through cleavable disulfide bonds.
Won Seok Seo, Jin Hyung Lee, Xiaoming Sun, Yoriyasu Suzuki, David Mann, Zhuang Liu, Masahiro Terashima, Philip C. Yang, Michael V. McConnell, Dwight G. Nishimura, and Hongjie Dai. “FeCo/graphitic-shell nanocrystals as advanced magnetic-resonance-imaging and near-infrared agents,” Nature Materials, VOL 5, 971, 2006 discloses the preparation of pure FeCo/graphitic carbon nanocrystals. These were PL-PEG functionalized for MRI imaging.
Nadine Wong Shi Kam, Zhuang Liu, and Hongjie Dai “Carbon Nanotubes as Intracellular Transporters for Proteins and DNA: An Investigation of the Uptake Mechanism and Pathway,” Angew. Chem. Int. Ed., 44, 1-6, 2005, discloses acid oxidized SWNTs, which were used for conjugation with proteins, and non-oxidized SWNTs, which were used to complex with DNA molecules.
Nadine Wong Shi Kam and Hongjie Dai “Carbon Nanotubes as Intracellular Protein Transporters: Generality and Biological Functionality,” J. Am. Chem. Soc., 127, 6021-6026, 2005, discloses that SWNTs are generic intracellular transporters for various types of proteins (less than or equal to 80 kD) noncovalently and non-specifically bound to nanotube sidewalls.
Nadine Wong Shi Kam, Theodore C. Jessop, Paul A. Wender, and Hongjie Dai, “Nanotube Molecular Transporters: Internalization of Carbon Nanotube-Protein Conjugates into Mammalian Cells,” J. Am. Chem. Soc., 126, 6850-6851 2004, discloses the preparation of SWNTs refluxed in HNO3 followed by sonication, resulting in negatively charged acidic groups on the surface, which were used to couple various molecules such as biotin.